A serious problem of a transplantation of a tissue or an organ which is frequently performed in recent years is a rejection symptom for excluding a transplanted part after an operation. Prevention of the rejection symptom is very important for a success of the transplantation.
Various immunosuppressors such as azathioprine, corticoid, Cyclosporin A, Tacrolimus and the like are developed and come into practical use for prevention and a treatment of a rejection symptom against a transplantation of an organ or a tissue or a graft-versus-host reaction which is caused by a bone marrow transplantation. But they are not so satisfactory in view of their effects and side effects.
Allergic diseases such as atopic dermatitis, allergic rhinitis, bronchial asthma, allergic conjunctivitis and the like globally tend to increase in recent years and become serious problems. The conventional antiinflammatory agents are suppressors of releasing chemical mediators from mast cells, receptor inhibitors of the chemical mediators released, suppressors of allergic inflammation reaction or the like. All of these are agents for symptomatic therapy and are not fundamental therapeutic agents for allergic diseases.
As an fundamental therapeutic agent for allergic diseases, a suppressor of the IgE antibody production has been expected.
One of compounds which have a suppressive effect on the IgE production is Suplatast Tosilate (IPD-1151-T). This is reported to act on T cell of type 2 (Th2 cell) to suppress the IL-4 production and to suppress a differentiation of B cells to IgE antibody-producing cells (Jpn. Pharmacol. (1993) 61, 31–39).
As compounds which directly act on B cells to suppress the IgE antibody production, for example, DSCG (Intal) or Nedcromil sodium which are degranulation inhibitors of mast cells are exemplified. These are reported to inhibit a class-switch of B cells (J. Exp. Med. (1994) 180: 663–671, J. Allergy Clin. Immunol. (1996) 97: 1141–1150). In J. Med. Chem. (1997) 40: 395–407, a compound which directly acts on B cells to suppress the IgE production is described.
Because immune globulins are necessary for phylaxis and a suppression of immune globulins other than IgE antibody is not preferable, an inhibitor which has a high selectivity to IgE and a potent effect has been desired.
The compounds which have an antiinflammatory effect and ortho-terphenyl structure are described in JP-A 60-13730, J. Med. Chem. (1996) 39: 1846–1856 and WO96/10012, and the compounds which have the same effect and biphenyl structure are described in JP-B 43-19935, JP-A 62-294650 and WO96/18606.
The compounds which have para-terphenyl structure are described in Chemical & Pharmaceutical Bulletin, 24 (4), 613–620 (1976), The Journal of Antibiotics, 32 (6), 559–564 (1979) and Agricultural Biological Chemistry, 49 (3), 867–868 (1985) but an immunosuppressive or antiinflammatory effect of these compounds is not described at all.